Oral Abstracts

Abstract

Background: Progressive familial intrahepatic cholestasis (PFIC) is characterized by high serum bile acids (sBAs), severe pruritus, and liver disease that worsens over time. Previous studies have shown a correlation between cholestatic pruritus and peripheral blood autotaxin (ATX) levels. ATX is also involved in the production of lysophosphatidic acid, another possible pruritic mediator, and nonclinical data suggest that sBAs may alter ATX activity. In the phase 3 PEDFIC 1 and PEDFIC 2 studies, levels of ATX, pruritus, and sBAs were assessed in patients with PFIC treated with odevixibat, an ileal bile acid transporter inhibitor. Here, we explored the relationships between these parameters using pooled data from these studies. Methods: In PEDFIC 1, children with PFIC received placebo or odevixibat 40 or 120 μg/kg/day for 24 weeks. PEDFIC 2 is an ongoing, 72-week extension study in patients of any age with PFIC; all patients in PEDFIC 2 receive odevixibat 120 μg/kg/day. This pooled analysis spans from patients’ first-ever dose of odevixibat to a data cutoff date of July 15, 2020. Caregivers evaluated patients’ pruritus using the validated PRUCISION scale (range: 0–4; higher scores indicate worse symptoms). Relationships between change from baseline in ATX, pruritus, and percent change from baseline in sBAs were assessed as post hoc analyses. Results: At the data cutoff date, 77 patients had received odevixibat (median exposure: 37 weeks). Most patients (88%) were continuing on treatment. Mean values for ATX, pruritus, and sBAs prior to the first dose of odevixibat (ie, baseline) are given in the Table. During treatment with odevixibat, decreases from baseline were observed in ATX levels, pruritus scores, and sBAs (Table). There was a strong correlation between change from baseline in ATX and percent change in sBAs at weeks 25–48 (Table). Moderate correlations were observed between changes from baseline in ATX and pruritus and between changes in pruritus and percent changes in sBAs (Table). Among all 77 patients in this analysis, 18 patients had any treatment-emergent events of diarrhea; all were non-severe and resolved. Conclusion: Odevixibat treatment reduced ATX, pruritus, and sBAs, and significant correlations were observed between reductions in each pair of these parameters. Odevixibat was also generally well tolerated. Odevixibat may be a potential noninvasive treatment option to alleviate critical signs and symptoms of disease in patients with PFIC.